Olfactory-trigeminal integration in the primary olfactory cortex.

Humans naturally integrate signals from the olfactory and intranasal trigeminal systems. A tight interplay has been demonstrated between these two systems, and yet the neural circuitry mediating olfactory-trigeminal (OT) integration remains poorly understood. Using functional magnetic resonance imaging (fMRI), combined with psychophysics, this study investigated the neural mechanisms underlying OT integration. Fifteen participants with normal olfactory function performed a localization task with air-puff stimuli, phenylethyl alcohol (PEA; rose odor), or a combination thereof while being scanned. The ability to localize PEA to either nostril was at chance. Yet, its presence significantly improved the localization accuracy of weak, but not strong, air-puffs, when both stimuli were delivered concurrently to the same nostril, but not when different nostrils received the two stimuli. This enhancement in localization accuracy, exemplifying the principles of spatial coincidence and inverse effectiveness in multisensory integration, was associated with multisensory integrative activity in the primary olfactory (POC), orbitofrontal (OFC), superior temporal (STC), inferior parietal (IPC) and cingulate cortices, and in the cerebellum. Multisensory enhancement in most of these regions correlated with behavioral multisensory enhancement, as did increases in connectivity between some of these regions. We interpret these findings as indicating that the POC is part of a distributed brain network mediating integration between the olfactory and trigeminal systems. PRACTITIONER POINTS: Psychophysical and neuroimaging study of olfactory-trigeminal (OT) integration. Behavior, cortical activity, and network connectivity show OT integration. OT integration obeys principles of inverse effectiveness and spatial coincidence. Behavioral and neural measures of OT integration are correlated.

Toward rational use of cognitive training in those with mild cognitive impairment.

The term cognitive training includes a range of techniques that hold potential for treating cognitive impairment caused by neurologic injury and disease. Our central premise is that these techniques differ in their mechanisms of action and therefore engage distinct brain regions (or neural networks). We support this premise using data from a single-blind randomized-controlled trial in which patients with mild cognitive impairment were randomized to either mnemonic strategy training (MST) or spaced retrieval training (SRT) as they learned ecologically relevant object-location associations. Both training approaches were highly effective in the short term, but MST demonstrated a clear advantage after days to weeks. MST also increased activation in and functional connectivity between frontal, temporal, and parietal regions as well as the hippocampus. In contrast, patterns of reduced activation and functional connectivity were evident following SRT. These findings support the rational development of cognitive training techniques.

Consistency and strength of grapheme-color associations are separable aspects of synesthetic experience.

Consistency of synesthetic associations over time is a widely used test of synesthesia. Since many studies suggest that consistency is not a completely reliable feature, we compared the consistency and strength of synesthetes' grapheme-color associations. Consistency was measured by scores on the Synesthesia Battery and by the Euclidean distance in color space for the specific graphemes tested for each participant. Strength was measured by congruency magnitudes on the Implicit Association Test. The strength of associations was substantially greater for synesthetes than non-synesthetes, suggesting that this is a novel, objective marker of synesthesia. Although, intuitively, strong associations should also be consistent, consistency and strength were uncorrelated, indicating that they are likely independent, at least for grapheme-color synesthesia. These findings have implications for our understanding of synesthesia and for estimates of its prevalence since synesthetes who experience strong, but inconsistent, associations may not be identified by tests that focus solely on consistency.

Primary motor cortical activity during unimanual movements with increasing demand on precision.

In functional magnetic resonance imaging (fMRI) studies, performance of unilateral hand movements is associated with primary motor cortex activity ipsilateral to the moving hand (M1ipsi), in addition to contralateral activity (M1contra). The magnitude of M1ipsi activity increases with the demand on precision of the task. However, it is unclear how demand-dependent increases in M1ipsi recruitment relate to the control of hand movements. To address this question, we used fMRI to measure blood oxygenation level-dependent (BOLD) activity during performance of a task that varied in demand on precision. Participants (n = 23) manipulated an MRI-compatible joystick with their right or left hand to move a cursor into targets of different sizes (small, medium, large, extra large). Performance accuracy, movement time, and number of velocity peaks scaled with target size, whereas reaction time, maximum velocity, and initial direction error did not. In the univariate analysis, BOLD activation in M1contra and M1ipsi was higher for movements to smaller targets. Representational similarity analysis, corrected for mean activity differences, revealed multivoxel BOLD activity patterns during movements to small targets were most similar to those for medium targets and least similar to those for extra-large targets. Only models that varied with demand (target size, performance accuracy, and number of velocity peaks) correlated with the BOLD dissimilarity patterns, though differently for right and left hands. Across individuals, M1contra and M1ipsi similarity patterns correlated with each other. Together, these results suggest that increasing demand on precision in a unimanual motor task increases M1 activity and modulates M1 activity patterns.NEW & NOTEWORTHY Contralateral primary motor cortex (M1) predominantly controls unilateral hand movements, but the role of ipsilateral M1 is unclear. We used functional magnetic resonance imaging (fMRI) to investigate how M1 activity is modulated by unimanual movements at different levels of demand on precision. Our results show that task characteristics related to demand on precision influence bilateral M1 activity, suggesting that in addition to contralateral M1, ipsilateral M1 plays a key role in controlling hand movements to meet performance precision requirements.

Alterations of resting-state fMRI measurements in individuals with cervical dystonia.

Cervical dystonia (CD) is a neurological disorder with typical symptoms of involuntary and abnormal movements and postures of the head. CD-associated alterations of functional brain networks have not been well characterized. Previous studies of CD using resting-state functional MRI (rfMRI) are limited in two aspects: (i) the analyses were not directly focused on the functional brain network related to head movement and (ii) rfMRI measurements other than functional connectivity (FC) were not investigated. The present study examined alterations of FC in CD by capitalizing on newly identified brain regions supporting isometric head rotation (Prudente et al.: J Neurosci 35 (2015) 9163-9172). In addition to FC, which only reflects inter-regional signal synchronization, local, or intraregional alterations were also examined using rfMRI measurements of the fractional amplitude of low-frequency fluctuations and regional homogeneity (ReHo). Finally, with alterations of different rfMRI measures identified, a support vector machine (SVM) learning algorithm was implemented for group classification. The results revealed both inter- (FC) and intra-regional (ReHo) alterations extensively distributed in both cortical and subcortical structures; and common alterations of these measures were identified bilaterally in the postcentral gyrus as well as in the basal ganglia and thalamus. Of the rfMRI features examined, seven of them (four FC and three ReHo measures) survived the SVM procedure of recursive feature elimination and together provided the highest group classification accuracy of 90.6%. The present findings extend previous studies of rfMRI in CD and offer insight into the underlying pathophysiology of the disorder in relation to network dysfunction and somatosensory disturbances. Hum Brain Mapp 38:4098-4108, 2017. © 2017 Wiley Periodicals, Inc.

Enhanced verbal abilities in the congenitally blind.

Numerous studies have found that congenitally blind individuals have better verbal memory than their normally sighted counterparts. However, it is not known whether this reflects superiority of verbal or memory abilities. In order to distinguish between these possibilities, we tested congenitally blind participants and normally sighted control participants, matched for age and education, on a range of verbal and spatial tasks. Congenitally blind participants were significantly better than sighted controls on all the verbal tasks but the groups did not differ significantly on the spatial tasks. Thus, the congenitally blind appear to have superior verbal, but not spatial, abilities. This may reflect greater reliance on verbal information and the involvement of visual cortex in language processing in the congenitally blind.

Patterns of effective connectivity during memory encoding and retrieval differ between patients with mild cognitive impairment and healthy older adults.

Previous research has shown that there is considerable overlap in the neural networks mediating successful memory encoding and retrieval. However, little is known about how the relevant human brain regions interact during these distinct phases of memory or how such interactions are affected by memory deficits that characterize mild cognitive impairment (MCI), a condition that often precedes dementia due to Alzheimer's disease. Here we employed multivariate Granger causality analysis using autoregressive modeling of inferred neuronal time series obtained by deconvolving the hemodynamic response function from measured blood oxygenation level-dependent (BOLD) time series data, in order to examine the effective connectivity between brain regions during successful encoding and/or retrieval of object location associations in MCI patients and comparable healthy older adults. During encoding, healthy older adults demonstrated a left hemisphere dominant pattern where the inferior frontal junction, anterior intraparietal sulcus (likely involving the parietal eye fields), and posterior cingulate cortex drove activation in most left hemisphere regions and virtually every right hemisphere region tested. These regions are part of a frontoparietal network that mediates top-down cognitive control and is implicated in successful memory formation. In contrast, in the MCI patients, the right frontal eye field drove activation in every left hemisphere region examined, suggesting reliance on more basic visual search processes. Retrieval in the healthy older adults was primarily driven by the right hippocampus with lesser contributions of the right anterior thalamic nuclei and right inferior frontal sulcus, consistent with theoretical models holding the hippocampus as critical for the successful retrieval of memories. The pattern differed in MCI patients, in whom the right inferior frontal junction and right anterior thalamus drove successful memory retrieval, reflecting the characteristic hippocampal dysfunction of these patients. These findings demonstrate that neural network interactions differ markedly between MCI patients and healthy older adults. Future efforts will investigate the impact of cognitive rehabilitation of memory on these connectivity patterns.

Analysis of haptic information in the cerebral cortex.

Haptic sensing of objects acquires information about a number of properties. This review summarizes current understanding about how these properties are processed in the cerebral cortex of macaques and humans. Nonnoxious somatosensory inputs, after initial processing in primary somatosensory cortex, are partially segregated into different pathways. A ventrally directed pathway carries information about surface texture into parietal opercular cortex and thence to medial occipital cortex. A dorsally directed pathway transmits information regarding the location of features on objects to the intraparietal sulcus and frontal eye fields. Shape processing occurs mainly in the intraparietal sulcus and lateral occipital complex, while orientation processing is distributed across primary somatosensory cortex, the parietal operculum, the anterior intraparietal sulcus, and a parieto-occipital region. For each of these properties, the respective areas outside primary somatosensory cortex also process corresponding visual information and are thus multisensory. Consistent with the distributed neural processing of haptic object properties, tactile spatial acuity depends on interaction between bottom-up tactile inputs and top-down attentional signals in a distributed neural network. Future work should clarify the roles of the various brain regions and how they interact at the network level.

Synesthesia strengthens sound-symbolic cross-modal correspondences.

Synesthesia is a phenomenon in which an experience in one domain is accompanied by an involuntary secondary experience in another, unrelated domain; in classical synesthesia, these associations are arbitrary and idiosyncratic. Cross-modal correspondences refer to universal associations between seemingly unrelated sensory features, e.g., auditory pitch and visual size. Some argue that these phenomena form a continuum, with classical synesthesia being an exaggeration of universal cross-modal correspondences, whereas others contend that the two are quite different, since cross-modal correspondences are non-arbitrary, non-idiosyncratic, and do not involve secondary experiences. Here, we used the implicit association test to compare synesthetes' and non-synesthetes' sensitivity to cross-modal correspondences. We tested the associations between auditory pitch and visual elevation, auditory pitch and visual size, and sound-symbolic correspondences between auditory pseudowords and visual shapes. Synesthetes were more sensitive than non-synesthetes to cross-modal correspondences involving sound-symbolic, but not low-level sensory, associations. We conclude that synesthesia heightens universally experienced cross-modal correspondences, but only when these involve sound symbolism. This is only partly consistent with the idea of a continuum between synesthesia and cross-modal correspondences, but accords with the idea that synesthesia is a high-level, post-perceptual phenomenon, with spillover of the abilities of synesthetes into domains outside their synesthesias. To our knowledge, this is the first demonstration that synesthetes, relative to non-synesthetes, experience stronger cross-modal correspondences outside their synesthetic domains.

Neural changes with tactile learning reflect decision-level reweighting of perceptual readout.

Despite considerable work, the neural basis of perceptual learning remains uncertain. For visual learning, although some studies suggested that changes in early sensory representations are responsible, other studies point to decision-level reweighting of perceptual readout. These competing possibilities have not been examined in other sensory systems, investigating which could help resolve the issue. Here we report a study of human tactile microspatial learning in which participants achieved >six-fold decline in acuity threshold after multiple training sessions. Functional magnetic resonance imaging was performed during performance of the tactile microspatial task and a control, tactile temporal task. Effective connectivity between relevant brain regions was estimated using multivariate, autoregressive models of hidden neuronal variables obtained by deconvolution of the hemodynamic response. Training-specific increases in task-selective activation assessed using the task × session interaction and associated changes in effective connectivity primarily involved subcortical and anterior neocortical regions implicated in motor and/or decision processes, rather than somatosensory cortical regions. A control group of participants tested twice, without intervening training, exhibited neither threshold improvement nor increases in task-selective activation. Our observations argue that neuroplasticity mediating perceptual learning occurs at the stage of perceptual readout by decision networks. This is consonant with the growing shift away from strictly modular conceptualization of the brain toward the idea that complex network interactions underlie even simple tasks. The convergence of our findings on tactile learning with recent studies of visual learning reconciles earlier discrepancies in the literature on perceptual learning.

Oscillatory activity in neocortical networks during tactile discrimination near the limit of spatial acuity.

Oscillatory interactions within functionally specialized but distributed brain regions are believed to be central to perceptual and cognitive functions. Here, using human scalp electroencephalography (EEG) recordings combined with source reconstruction techniques, we study how oscillatory activity functionally organizes different neocortical regions during a tactile discrimination task near the limit of spatial acuity. While undergoing EEG recordings, blindfolded participants felt a linear three-dot array presented electromechanically, under computer control, and reported whether the central dot was offset to the left or right. The average brain response differed significantly for trials with correct and incorrect perceptual responses in the timeframe approximately between 130 and 175ms. During trials with correct responses, source-level peak activity appeared in the left primary somatosensory cortex (SI) at around 45ms, in the right lateral occipital complex (LOC) at 130ms, in the right posterior intraparietal sulcus (pIPS) at 160ms, and finally in the left dorsolateral prefrontal cortex (dlPFC) at 175ms. Spectral interdependency analysis of activity in these nodes showed two distinct distributed networks, a dominantly feedforward network in the beta band (12-30Hz) that included all four nodes and a recurrent network in the gamma band (30-100Hz) that linked SI, pIPS and dlPFC. Measures of network activity in both bands were correlated with the accuracy of task performance. These findings suggest that beta and gamma band oscillatory networks coordinate activity between neocortical regions mediating sensory and cognitive processing to arrive at tactile perceptual decisions.

Multisensory and lexical information in speech perception.

Both multisensory and lexical information are known to influence the perception of speech. However, an open question remains: is either source more fundamental to perceiving speech? In this perspective, we review the literature and argue that multisensory information plays a more fundamental role in speech perception than lexical information. Three sets of findings support this conclusion: first, reaction times and electroencephalographic signal latencies indicate that the effects of multisensory information on speech processing seem to occur earlier than the effects of lexical information. Second, non-auditory sensory input influences the perception of features that differentiate phonetic categories; thus, multisensory information determines what lexical information is ultimately processed. Finally, there is evidence that multisensory information helps form some lexical information as part of a phenomenon known as sound symbolism. These findings support a framework of speech perception that, while acknowledging the influential roles of both multisensory and lexical information, holds that multisensory information is more fundamental to the process.

Physical activity is associated with behavioral and neural changes across the lifespan.

Physical activity is known to positively impact brain structure and function, but its effects on resting-state functional connectivity (rsFC) and its relationship with complex tasks as a function of age remain unclear. Here, we address these issues in a large population-based sample (N = 540) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) repository. We relate levels of physical activity to rsFC patterns in magnetoencephalographic (MEG) and functional magnetic resonance imaging (fMRI) data, and to measures of executive function and visuomotor adaptation, across the lifespan. We show that higher self-reported daily physical activity is associated with lower alpha-band (8-12 Hz) global coherence, indicating weaker synchrony of neural oscillations in this band. Physical activity affected between-network connectivity of resting-state functional networks, although its effects on individual networks did not survive correction for multiple comparisons. Furthermore, our results indicate that greater engagement in day-to-day physical activity is associated with better visuomotor adaptation, across the lifespan. Overall, our findings indicate that rsFC metrics indexed by MEG and fMRI are sensitive indicators of the brain's response to physical activity, and that a physically active lifestyle affects multiple aspects of neural function across the lifespan.

Neural Basis Of Sound-Symbolic Pseudoword-Shape Correspondences.

Non-arbitrary mapping between the sound of a word and its meaning, termed sound symbolism, is commonly studied through crossmodal correspondences between sounds and visual shapes, e.g., auditory pseudowords, like 'mohloh' and 'kehteh', are matched to rounded and pointed visual shapes, respectively. Here, we used functional magnetic resonance imaging (fMRI) during a crossmodal matching task to investigate the hypotheses that sound symbolism (1) involves language processing; (2) depends on multisensory integration; (3) reflects embodiment of speech in hand movements. These hypotheses lead to corresponding neuroanatomical predictions of crossmodal congruency effects in (1) the language network; (2) areas mediating multisensory processing, including visual and auditory cortex; (3) regions responsible for sensorimotor control of the hand and mouth. Right-handed participants ( n = 22) encountered audiovisual stimuli comprising a simultaneously presented visual shape (rounded or pointed) and an auditory pseudoword ('mohloh' or 'kehteh') and indicated via a right-hand keypress whether the stimuli matched or not. Reaction times were faster for congruent than incongruent stimuli. Univariate analysis showed that activity was greater for the congruent compared to the incongruent condition in the left primary and association auditory cortex, and left anterior fusiform/parahippocampal gyri. Multivoxel pattern analysis revealed higher classification accuracy for the audiovisual stimuli when congruent than when incongruent, in the pars opercularis of the left inferior frontal (Broca's area), the left supramarginal, and the right mid-occipital gyri. These findings, considered in relation to the neuroanatomical predictions, support the first two hypotheses and suggest that sound symbolism involves both language processing and multisensory integration. HIGHLIGHTS: fMRI investigation of sound-symbolic correspondences between auditory pseudowords and visual shapesFaster reaction times for congruent than incongruent audiovisual stimuliGreater activation in auditory and visual cortices for congruent stimuliHigher classification accuracy for congruent stimuli in language and visual areasSound symbolism involves language processing and multisensory integration.

Neural basis of sound-symbolic pseudoword-shape correspondences.

Non-arbitrary mapping between the sound of a word and its meaning, termed sound symbolism, is commonly studied through crossmodal correspondences between sounds and visual shapes, e.g., auditory pseudowords, like 'mohloh' and 'kehteh', are matched to rounded and pointed visual shapes, respectively. Here, we used functional magnetic resonance imaging (fMRI) during a crossmodal matching task to investigate the hypotheses that sound symbolism (1) involves language processing; (2) depends on multisensory integration; (3) reflects embodiment of speech in hand movements. These hypotheses lead to corresponding neuroanatomical predictions of crossmodal congruency effects in (1) the language network; (2) areas mediating multisensory processing, including visual and auditory cortex; (3) regions responsible for sensorimotor control of the hand and mouth. Right-handed participants (n = 22) encountered audiovisual stimuli comprising a simultaneously presented visual shape (rounded or pointed) and an auditory pseudoword ('mohloh' or 'kehteh') and indicated via a right-hand keypress whether the stimuli matched or not. Reaction times were faster for congruent than incongruent stimuli. Univariate analysis showed that activity was greater for the congruent compared to the incongruent condition in the left primary and association auditory cortex, and left anterior fusiform/parahippocampal gyri. Multivoxel pattern analysis revealed higher classification accuracy for the audiovisual stimuli when congruent than when incongruent, in the pars opercularis of the left inferior frontal (Broca's area), the left supramarginal, and the right mid-occipital gyri. These findings, considered in relation to the neuroanatomical predictions, support the first two hypotheses and suggest that sound symbolism involves both language processing and multisensory integration.

Mnemonic strategy training partially restores hippocampal activity in patients with mild cognitive impairment.

Learning and memory deficits typify patients with mild cognitive impairment (MCI) and are generally attributed to medial temporal lobe dysfunction. Although the hippocampus is perhaps the most commonly studied neuroanatomical structure in these patients, there have been few attempts to identify rehabilitative interventions that facilitate its functioning. Here, we present results from a randomized, controlled, single-blind study in which patients with MCI and healthy elderly controls (HEC) were randomized to either three sessions of mnemonic strategy training (MS) or a matched-exposure control group (XP). All participants underwent pre- and posttraining fMRI scanning as they encoded and retrieved object-location associations. For the current report, fMRI analyses were restricted to the hippocampus, as defined anatomically. Before training, MCI patients showed reduced hippocampal activity during both encoding and retrieval, relative to HEC. Following training, the MCI MS group demonstrated increased activity during both encoding and retrieval. There were significant differences between the MCI MS and MCI XP groups during retrieval, especially within the right hippocampus. Thus, MS facilitated hippocampal functioning in a partially restorative manner. We conclude that cognitive rehabilitation techniques may help mitigate hippocampal dysfunction in MCI patients.

A rigorous approach for testing the constructionist hypotheses of brain function.

Although the target article provides strong evidence against the locationist view, evidence for the constructionist view is inconclusive, because co-activation of brain regions does not necessarily imply connectivity between them. We propose a rigorous approach wherein connectivity between co-activated regions is first modeled using exploratory Granger causality, and then confirmed using dynamic causal modeling or Bayesian modeling.

Cross-Modal Interactions of the Tactile System.

The sensory systems responsible for perceptions of touch, vision, hearing, etc. have traditionally been regarded as mostly separate, only converging at late stages of processing. Contrary to this dogma, recent work has shown that interactions between the senses are robust and abundant. Touch and vision are both commonly used to obtain information about a number of object properties, and share perceptual and neural representations in many domains. Additionally, visuotactile interactions are implicated in the sense of body ownership, as revealed by powerful illusions that can be evoked by manipulating these interactions. Touch and hearing both rely in part on temporal frequency information, leading to a number of audiotactile interactions reflecting a good deal of perceptual and neural overlap. The focus in sensory neuroscience and psychophysics is now on characterizing the multisensory interactions that lead to our panoply of perceptual experiences.

Perceptual Dissimilarity Analysis Distinguishes Grapheme-Color Synesthetes from Nonsynesthetes.

Synesthetes can be distinguished from nonsynesthetes on a variety of experimental tasks because their concurrent synesthetic experiences can affect task performance if these experiences match or conflict with some aspect of the stimulus. Here, we tested grapheme-color synesthetes and nonsynesthetic control participants using a novel perceptual similarity task to assess whether synesthetes' concurrent color experiences influence perceived grapheme similarity. Participants iteratively arranged graphemes and, separately, their associated synesthetic colors in a display, such that similar items were placed close together and dissimilar items further apart. The resulting relative inter-item distances were used to calculate the pair-wise (dis)similarity between items in the set, and thence to create separate perceptual representational dissimilarity matrices (RDMs) for graphemes and colors, on an individual basis. On the assumption that synesthetes' similarity judgments for graphemes would be influenced by their concurrent color experiences, we predicted that grapheme and color RDMs would be more strongly correlated for synesthetes than nonsynesthetes. We found that the mean grapheme-color RDM correlation was indeed significantly higher in synesthetes than nonsynesthetes; in addition, synesthetes' grapheme-color RDM correlations were more likely to be individually statistically significant, even after correction for multiple tests, than those of nonsynesthetes. Importantly, synesthetes' grapheme-color RDM correlations were scaled with the consistency of their grapheme-color associations as measured by their Synesthesia Battery (SB) scores. By contrast, the relationship between SB scores and grapheme-color RDM correlations for nonsynesthetes was not significant. Thus, dissimilarity analysis quantitatively distinguished synesthetes from nonsynesthetes, in a way that meaningfully reflects a key aspect of synesthetic experience.